Scoping Review of Diagnostic Strategies for Carpal Tunnel Syndrome and Compressive Median Neuropathy at the Carpal Tunnel

Abstract

Background

Symptoms and pathophysiology are often discordant. To better understand areas of debate regarding diagnosis of carpal tunnel syndrome (CTS) and compressive median neuropathy at the carpal tunnel (CMNCT), we assessed (1) Do studies distinguish CTS (illness) and CMNCT (pathophysiology)? (2) What aspects of diagnosis are evaluated in studies of CTS and CMNCT? and (3) What diagnostic strategies are used for CTS?.

Methods

We identified 186 consecutive studies that addressed diagnostic strategies for CTS or CMNCT and assessed the aspects of diagnosis addressed, the diagnostic strategies addressed, the distinction between CTS and CMNCT, whether CTS or CMNCT was the subject of study, and the reference standard for CTS or CMNCT diagnosis.

Results

Seventy studies (38%) distinguished CTS and CMNCT. Most evaluated measures of pathophysiology either in isolation (68%) or combined with other factors (17%). Among the 128 studies that addressed diagnosis of CTS, the majority (66%) used a reference standard that included both symptoms and measures of pathophysiology, and the others used symptoms and signs alone.

Discussion

In diagnostic experiments, separation of symptoms and pathophysiology has the potential to identify factors associated with their discordance. Better understanding of such discordance could limit misattribution of symptoms to pathophysiology, misdiagnosis, and overtreatment.

Introduction

Diagnostic strategies have potential for harm and potential for benefit. ¹ Potential harms include overdiagnosis and overtreatment. Diagnostic strategies are also relevant in studies of association or etiology. Carpal tunnel syndrome (CTS) is the set of symptoms and signs characteristic of compressive median neuropathy at the carpal tunnel (CMNCT). There is a wide range of diagnostic strategies for both CTS and CMNCT. There is no consensus reference standard for diagnosis of CMNCT, particularly in mild-to-moderate cases. ²

CTS is sometimes diagnosed even when electrodiagnostic tests find no evidence of CMNCT, which risks overdiagnosis and inaccurate etiological associations. To better understand the areas of debate of diagnosis of CTS and CMNCT, we undertook a scoping review of the type and frequency of diagnostic strategies.

This scoping review of diagnostic methods for CTS and CMNCT addressed the following questions: (1) Do studies distinguish CMNCT (pathophysiology) and CTS (illness)? (2) What aspects of diagnosis are evaluated in studies of CTS and CMNCT? and (3) What diagnostic strategies are used for CTS?

Material and Methods

The protocol for this scoping review was registered on OSF Registries. It can be accessed at https://doi.org/10.17605/OSF.IO/ZMRX8. Results for this study were reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) extension for scoping reviews. ³

Search Approach

The text words found in titles and abstracts, along with index terms used to describe articles, were utilized to formulate a comprehensive search strategy for Ovid (Table S1). This strategy included the medical subject heading “Carpal Tunnel Syndrome” and subheadings “diagnosis” and “diagnostic imaging.” Studies were eligible for inclusion if they addressed diagnostic strategies for CMNCT or CTS.

We considered studies published in English from January 1st, 2010, to February 16th, 2023. Animal studies, reviews, opinions, editorials, perspectives, viewpoints, news articles, and conference articles or abstracts were excluded. Studies that did not specifically name the diagnostic procedures performed or primarily evaluated methods or tools for severity grading or characterization of disease for CMNCT or CTS were also excluded.

Selection of Studies/Evidence Sources

Titles and abstracts were screened based on the inclusion criteria for the review. Full-text articles were assessed for potentially relevant sources, and their citation details were imported into EndNote. One author did both the screening of the titles/abstracts and full texts of the studies.

After screening the abstracts of 1426 articles identified in the search, 400 were selected for a comprehensive full-text review, and 186 were included in this study (Figure 1). Among the 186 studies, 81 were comparative cohort studies, 45 were prospective cohort studies, 26 were case-control studies, 22 were cross-sectional studies, 8 were retrospective cohort studies, one was a retrospective comparative cohort study, one was a retrospective cross-sectional study, and one was a survey.

Figure 1.

Flow diagram showing the search strategy and study selection.

Data Extraction

Two authors reviewed the full texts of the studies and extracted data from the articles that met the inclusion criteria. Disputes regarding study inclusion or extracted data were settled through discussion between the two authors. The extracted characteristics for each study encompassed details such as the aspects of diagnosis addressed, the diagnostic strategies addressed, the distinction between CMNCT and CTS, whether CMNCT or CTS was the subject of study, and the reference standard for CMNCT or CTS diagnosis (Table S2).

Studies were interpreted as addressing CMNCT if electrodiagnosis was the reference standard. Studies that incorporated signs and symptoms into the reference standard were interpreted as addressing CTS.

Studies were regarded as distinguishing between CMNCT and CTS if: (1) measured pathophysiology was considered separately from symptoms and signs and (2) people with CTS symptoms and normal electrophysiology or abnormal electrophysiology and no symptoms of CTS were considered.

Results

Do Studies Distinguish CMNCT (Pathophysiology) and CTS (Illness)?

Of the 186 studies, 128 (69%) addressed CTS, 52 (28%) addressed CMNCT, four (2%) did not clearly define the study focus, and two (1%) studies addressed both CMNCT and CTS. One of the four studies conflated CTS and CMNCT based on the absence of a consensus reference standard and used latent class analysis to identify classes of diagnostic probabilities. ⁴ Only 70 studies (38%) provided explicit criteria distinguishing median neuropathy (CMNCT) from characteristic symptoms and signs (CTS).

What Aspects of Diagnosis are Evaluated in Studies of CTS and CMNCT?

Ninety studies addressed imaging diagnosis (77 [86%] addressed ultrasound), 37 addressed electrophysiological diagnosis, 24 addressed physical examination diagnosis, 4 addressed questionnaire-based diagnosis, and 31 addressed a comparison of diagnostic techniques: imaging vs electrodiagnosis in 10 (10 of 10 addressing ultrasound), electrodiagnosis vs electrodiagnosis in 6, imaging vs imaging in 4 (3 of 4 addressing ultrasound), physical exam vs physical exam in 3, imaging vs questionnaire vs electrodiagnosis in 3 (3 of 3 addressing ultrasound), questionnaire vs electrodiagnosis in 2, physical exam vs electrodiagnosis in 2, and clinical history vs physical exam vs electrodiagnosis in 1.

Additional study questions addressed the correspondence of CMNCT severity with imaging findings (36 studies), correspondence of CMNCT severity with electrodiagnostic findings (10 studies), association of demographic factors with diagnostic test results (8 studies), determination of cutoff values for diagnosis (7 studies), correspondence of symptoms with pathophysiology (6 studies), correspondence of CMNCT severity with physical exam findings (6 studies), and correspondence of CMNCT severity with treatment outcomes (2 studies).

What Diagnostic Strategies are Used for CTS?

Among the studies that addressed CTS, 83 of 128 (65%) diagnosed CTS used a reference standard of a combination of electrodiagnostic studies (EDS) and signs and symptoms, 43 of 128 (34%) used only signs and symptoms, one of 128 (1%) used post-operative alleviation of paresthesia, and one of 128 (1%) used a combination of signs and symptoms, ultrasound, EDS, and post-operative symptom alleviation. Two studies separately addressed both CTS (signs and symptoms) and CMNCT (EDS). Among the four studies that did not clearly define the study focus, one (25%) used latent class analysis and three (75%) did not have a clear reference standard.

When evaluating the reference standards for CTS used in the 131 studies that compared two cohorts of patients, 66 studies (50%) applied the same reference standard to people with suspected CTS and volunteers with no symptoms, 49 (37%) did not apply the same reference standard to the two groups, and 16 studies (12%) did not clearly describe the reference standard applied to the volunteers.

Discussion

Background and Justification

Both a lack of distinction between symptoms (CTS) and pathophysiology (CMNCT) as well as a lack of consensus on reference standards for CTS and CMNCT hinder accurate diagnosis and potentially lead to over- or underdiagnosis and over- or undertreatment. To better understand areas of debate regarding diagnosis of CTS and CMNCT, this scoping review addressed three primary issues: approaches to the distinction between CMNCT (pathophysiology) and CTS (illness), aspects of diagnosis evaluated in studies of CTS and CMNCT, and the diagnostic strategies employed for CTS. We found that less than half the studies distinguished symptoms (CTS) from neuropathy (CMNCT), studies addressing imaging diagnosis (mostly ultrasound) were relatively common, and the reference standard for CTS and its application to cohorts designated as having and not having CTS was inconsistent.

Do Studies Distinguish CMNCT (Pathophysiology) and CTS (Illness)?

The finding that only 38% of studies explicitly distinguished between CMNCT and CTS points to important shortcomings in the conceptualization and study of median neuropathy. The common conflation of pathophysiology (CMNCT) and symptoms (CTS) is inaccurate. Many people have median neuropathy and no symptoms.^5-10 Others have symptoms and no measurable median neuropathy.^11-14 The inaccurate conflation of CMNCT and CTS can lead to misleading experiments in which the onset of symptoms is incorrectly equated with the onset of disease. We know that new symptoms from long-standing, gradual onset pathophysiology are often misinterpreted by humans as new pathophysiology.^15-17 If we want to understand factors causally associated with median neuropathy, we need to study objectively measurable neuropathy rather than symptoms. The inadherence to these principles has potential for harm from inappropriate causal links that demonize hand use in cherished occupational and avocational activities. Conflation of CTS and CMNCT may also increase the potential for harm due to over- or underdiagnosis and over- or undertreatment.

What Aspects of Diagnosis are Evaluated in Studies of CTS and CMNCT?

The observation that studies mostly focus on measures of pathophysiology on EDS, imaging, or examination is discordant with the tendency to conflate CTS (symptoms) and CMNCT (pathophysiology). A focus on measurable pathophysiology would seem to emphasize that symptoms may not correspond with pathophysiology and would seem to prioritize measures of pathophysiology. There are values and principles, either implicit or explicit, inherent in the questions asked by diagnostic studies and the degree to which CTS and CMNCT is emphasized in those studies. We encourage researchers to explicitly address the distinction between CTS and CMNCT, and to describe their definitions and measures. We also encourage researchers to explicitly state their principles and beliefs regarding the relative prioritizing of measurable pathophysiology or symptoms in diagnosis and treatment.

What Diagnostic Strategies are Used for CTS?

The observation that diagnosis of CTS included EDS abnormalities more often than not, and that different diagnostic reference standards are often applied to people with and without symptoms, again points to a potential overemphasis on symptoms. We know that gradual onset diseases such as carpal tunnel syndrome are often well accommodated, meaning that the sensations don’t register as a concern (a symptom). ¹⁸ For instance, the contralateral, asymptomatic median nerve is often abnormal on EDS.^5-10 New symptoms are often misperceived as new pathophysiology, even for long-standing gradual onset pathophysiologies.^15-17 In other words, the connections made by the human mind’s heuristics (mental short cuts) are often incorrect (cognitive errors). The tendency of the well-functioning human mind to err (cognitive bias) can be considered the foundation of the scientific method. In our opinion, the inclusion of objective measures of median neuropathy along with characteristic symptoms is unhelpful in experimental research where a clear delineation between pathophysiology and symptoms is important. Using a combination of measures of pathophysiology and symptoms and signs can also contribute to the inappropriate conflation of CTS and CMNCT. For diseases like diabetes and hypertension, disease-modifying treatment addresses measurable pathophysiology, regardless of symptoms. Likewise, carpal tunnel release is a disease-modifying treatment that can prevent loss of sensibility and palmar abduction weakness. This stands in contrast to the treatment of pain from arthritis, tendinopathy, and enthesopathy, common to musculoskeletal surgery, which is largely discretionary and preference sensitive. The treatment of CMNCT is arguably not discretionary. Rather than just addressing comfort, it can preserve useful sensibility.

Limitations

There are several limitations of the work to consider. First, the reliance on a single reviewer for screening titles/abstracts may have introduced some bias, although strict adherence to predefined inclusion and exclusion criteria helped ensure consistency throughout the process. And involvement of a second reviewer at the full-text stage made practical and effective use of researcher effort. Second, the interpretation of studies clearly distinguishing CMNCT from CTS was conceptual and contained an element of subjectivity, which could impact the accuracy of classification. On the other hand, the use of explicit criteria for distinguishing between CMNCT and CTS helped provide transparency and consistency in classification, reducing the potential for misinterpretation.

Conclusion

The findings in this scoping review of diagnostic studies demonstrate inadequate distinction of CMNCT and CTS and an overemphasis on symptoms in the study of median neuropathy in spite of the evidence of limited correspondence, pointing to the potential inappropriate conflation of CMNCT and CTS. A syndrome is the set of symptoms and signs characteristic of a disease, but we often use the term CTS when we mean CMNCT. The lack of a consensus reference standard for diagnosing CMNCT, particularly in mild-to-moderate cases, underscores the challenges in establishing a clear and universally accepted diagnostic approach. This ambiguity contributes to the potential harms associated with diagnostic strategies, such as overdiagnosis and overtreatment. Patients and clinicians might resolve this ambiguity by deciding, on principle, how to treat mild median neuropathy, likely with non-operative treatment (because mild median neuropathy is generally accommodated) and to limit potential unnecessary surgery. In the setting of experimental research, median neuropathy can be measured on its continuum rather than dichotomized. ²

Supplemental Material

Supplemental Material - Scoping Review of Diagnostic Strategies for Carpal Tunnel Syndrome and Compressive Median Neuropathy at the Carpal Tunnel

Supplemental Material for Scoping Review of Diagnostic Strategies for Carpal Tunnel Syndrome and Compressive Median Neuropathy at the Carpal Tunnel by Bryce Jensen, William Hlavinka, and David Ring in Montefiore Einstein Journal of Musculoskeletal Medicine and Surgery.